Differential induction of adenylyl cyclase supersensitivity by antiparkinson drugs acting as agonists at dopamine D1/D2/D3 receptors vs D2/D3 receptors only: Parallel observations from co-transfected human and native cerebral receptors

Aloisi, Gabriella; Silvano, Elena; Rossi, Mario; Millan, Mark J.; Maggio, Roberto

doi:10.1016/j.neuropharm.2010.10.018

Cited by 16 publications

(10 citation statements)

References 45 publications

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“…Long-term exposure to quinpirole, pramipexole and ropinirole (which possess negligible affinities for D (1) sites) elicited supersensitivity of adenyl cycles by interacting at D 1 /D 2 /D 3 receptors. Interpretation of these result suggests that ropinirole following chronic use may induce down regulation of D 2 receptors and central tolerance to its effects (Aloisi, Silvano, Rossi, Millan & Maggio, 2011). We have suggested earlier that supersensitivity will induce relapse of addictive behaviors (Blum et al, 2009).…”

Section: Discussionmentioning

confidence: 75%

Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT)

McLaughlin

Oscar‐Berman²,

Simpatico³

et al. 2013

Journal of Behavioral Addictions

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Background and aims:Many patients presenting multiple behaviors including drug and food abuse as well as other pathological repetitive unwanted activities such as gambling, self-mutilation and paraphilias may not be appropriately diagnosed. Here we present a case of a male presenting many of these seemingly diverse behaviors and finally diagnosed with reward deficiency syndrome (RDS) by his attending physician. Methods: The use of the dopamine agonist, ropinirole after two weeks showed improvement in terms of sexual behavior but tolerance set in and was discontinued especially when an infraction occurred with the patient's insurance. In this article, we carefully explore the potential of ropinirole to downregulate dopamine receptors causing adenylate cyclase receptor supersensitivity and tolerance a feature of neurotransmitter cross-talk. Based on previous scientific evidence showing KB220Z-nutrigenomic amino-acid therapy (NAAT) to rapidly (post one-hour) activate dopaminergic pathways in both the pre-frontal cortex cingulate gyrus (relapse loci) and ventral tegmental area-caudate-accumbens-putamen (craving and emotion loci) the patient was prescribed NAAT. Results and discussion: Within one week of utilization the repetitive paraphilia was eliminated. There were also a number of other positive effects such as enhanced focus that persisted even after the patient stopped using KB220Z suggesting neuroplasticity (e.g. altruistic thoughts). However, these observed profound benefits require more in-depth study, especially in a large cohort against a placebo. While this report focused on a rapid response rather than long-term benefits previously associated with NAAT, it is somewhat encouraging and longer term required follow-up and larger placebo controlled studies are warranted before any definitive conclusions could be gleaned from this case report.

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Section: Discussionmentioning

confidence: 75%

Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT)

McLaughlin

Oscar‐Berman²,

Simpatico³

et al. 2013

Journal of Behavioral Addictions

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“…CHO-D 3 -DHFRcells (from now on named CHO-D 3 ) were provided by Pierre Sokoloff (Sokoloff et al, 1992). CHO-D 2L and CHO-D 1 cells were generated by transfecting the human dopamine D 2L or human dopamine D 1 receptors, respectively, in wild type CHO cells (Aloisi et al, 2011). CHO-hM 4 (human muscarinic M 4 receptor) cells were prepared as described previously in Maggio et al, 1995.…”

Section: Stably-transfected Cho-d 3 Cho-d 2l Cho-d 1 and Cho-m 4 mentioning

confidence: 99%

Distinctive binding properties of the negative allosteric modulator, [ 3 H]SB269,652, at recombinant dopamine D 3 receptors

Fasciani

Pietrantoni

Rossi

et al. 2018

European Journal of Pharmacology

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Recently, employing radioligand displacement and functional coupling studies, we demonstrated that SB269,652 (N-[(1r,4r)-4-[2-(7-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide) interacts in an atypical manner with dopamine D receptor displaying a unique profile reminiscent of a negative allosteric ligand. Here, we characterized the binding of radiolabelled [H]SB269,652 to human dopamine D receptor stably expressed in Chinese Hamster Ovary cells. Under saturating conditions, SB269,652 showed a KD value of ≈ 1nM. Consistent with high selectivity for human dopamine D receptor, [H]SB269,652 binding was undetectable in cells expressing human dopamine D, D or D receptors and absent in synaptosomes from dopamine D receptor knockout vs. wild-type mice. In contrast to saturation binding experiments, the dissociation kinetics of [H]SB269,652 from human dopamine D receptors initiated with an excess of unlabelled ligand were best fitted by a bi-exponential binding model. Supporting the kinetic data, competition experiments with haloperidol, S33084 (a dopamine D receptor antagonist) or dopamine, were best described by a two-site model. In co-transfection experiments binding of SB269,652 to dopamine D receptor was able to influence the functional coupling of dopamine D receptor, supporting the notion that SB269,652 is a negative allosteric modulator across receptor dimers. However, because SB269,652 decreases the rate of [H]nemonapride dissociation, the present data suggest that SB269,652 behaves as a bitopic antagonist at unoccupied dopamine D receptor, binding simultaneously to both orthosteric and allosteric sites, and as a pure negative allosteric modulator when receptors are occupied and it can solely bind to the allosteric site.

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“…injections of the dopamine D 2 receptor agonist quinpirole results in an enhancement of the cAMP response of striatal neurons to activation of dopamine D 1 receptors (Gα s -coupled) in hamsters (Chester et al, 2006). Additionally, chronic treatment of mice with quinpirole or pramipexole for five weeks sensitizes neurons from the nucleus accumbens to dopamine-activated cAMP production (Aloisi et al, 2011). These studies indicate that prolonged activation of the dopamine D 2 receptor in rodents leads to heterologous sensitization of the dopamine D1 receptor-mediated activation of adenylyl cyclases.…”

Section: Heterologous Sensitization In Animalsmentioning

confidence: 99%

Gαi/o-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later

Brust

Conley

Watts

2015

European Journal of Pharmacology

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Heterologous sensitization of adenylyl cyclase (also referred to as superactivation, sensitization, or supersensitization of adenylyl cyclase) is a cellular adaptive response first described 40 years ago in the laboratory of Dr. Marshall Nirenberg. This apparently paradoxical cellular response occurs following persistent activation of Gαi/o-coupled receptors and causes marked enhancement in the activity of adenylyl cyclases, thereby increasing cAMP production. Since our last review in 2005, significant progress in the field has led to a better understanding of the relevance of, and the cellular biochemical processes that occur, during the development and expression of heterologous sensitization. In this review we will discuss the recent advancements in the field and the mechanistic hypotheses on heterologous sensitization.

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Differential induction of adenylyl cyclase supersensitivity by antiparkinson drugs acting as agonists at dopamine D1/D2/D3 receptors vs D2/D3 receptors only: Parallel observations from co-transfected human and native cerebral receptors

Cited by 16 publications

References 45 publications

Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT)

Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT)

Distinctive binding properties of the negative allosteric modulator, [ 3 H]SB269,652, at recombinant dopamine D 3 receptors

Gαi/o-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later

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